ABSTRACT Physicians trained in the identification and treatment of patients with unhealthy substance use continue to be in short supply, a problem that is exacerbated by an overdose epidemic driven by prescription drug abuse. Research and clinical skills are needed among three groups of physicians who are facing the current substance use epidemic: primary care physicians with patients experiencing unhealthy substance use; physicians caring for patients with HIV and Hepatitis C virus (HCV) infection; and those who treat patients with pain. This renewal grant application proposes funding for years 16-20 of the Clinical Addiction Research and Education (CARE) Program to expand upon previous successes to develop substance use disorder expertise among physician researchers and educators. The CARE Program has the following Specific Aims: (1a) To carry out a program in Addiction Medicine in order to train Chief Resident (CR) physician educators and their faculty mentors to teach state-of-the-art clinical care of patients with substance use and prescription drug abuse via continuation of the Chief Resident Immersion Training (CRIT) program. Enhanced topics in this application are safe and effective use of opioids for managing pain, addressing prescription drug abuse, and understanding the medical consequences of drug and alcohol use. (1b) To carry out a program in Addiction Medicine in order to prepare fellows from Infectious Disease (ID) and Pain Medicine specialties to incorporate substance use topics into their research by continuing to host the Fellow Immersion Training (FIT) program in conjunction with CRIT. Each fellow will develop an analytic plan and research proposal to investigate an addiction-related aspect of HIV, HCV, or prescription drug abuse/chronic pain. (2) To support medical trainees and early career physician faculty in the development of clinical addiction research careers by recruiting medical students, residents, fellows and junior faculty to be mentored by CARE Program faculty on addiction research studies. (3) To enable physicians and addiction researchers to be up-to-date on clinically relevant unhealthy substance use and addiction-related research ethics by producing and upgrading the research summary newsletter and website Alcohol, Other Drugs, and Health: Current Evidence (aodhealth.org), adding a focus on prescription drug abuse and fostering an online community. The CARE Program utilizes some of the most experienced of NIDA?s generalist physician investigators in a comprehensive effort to train a spectrum of physicians in clinical research methods and the medical care of patients with or at risk for drug use disorders. It will make important contributions to the development of the next generation of physician substance use researchers and to the dissemination of addiction research in order to provide better care for patients.